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Stand Up For Science

Post details: Mice show the way to safer stem cells!

02/03/09

Mice show the way to safer stem cells!

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You may remember that back in 2007 we reported on a scientific breakthrough that was making the headlines around the world, the development of induced pluripotent stem (iPS) cells, and more recently we have seen how Scotland is becoming a centre for stem cell research. It's therefore not a huge surprise to see Scottish scientists playing a key role in the latest iPS cell breakthrough, one that has once again been reported widely on television and in the newspapers.

iPS cells are adult cells that have been reprogrammed through genetic modification to take on the characteristics of embryonic stem cells, most importantly pluripotency; the ability of a cell to differentiate to become any adult cell type. The hope is that these iPS cells will ultimately be used to repair tissue damaged by accident or disease, and in the shorter term to produce better in vitro cell and tissue models of disease. A drawback with the iPS cells produced to date is that they are made using retrovirus vectors to deliver key genes required for pluripotency to the cells, and afterwards both the viral vectors and pluripotency genes remain integrated into the cell. There are concerns that both the pluripotency genes, especially one named c-Myc that is involved in several cancers, and the viral vectors used might behave unperedictibly with the risk that they might cause cancer in transplant patients. In the work reported in Nature (1) British scientists led by Dr Keisuke Kaji and their Canadian colleagues led by Professor Andras Nagy have got around this problem by using a non-virus vector that contains the pluripotency genes flanked by a sequences that enables them to cut the vector out of the genome, so that once the cells are in a pluripotent state the pluripotency genes can be removed from the genome and the cells differentiated into the required tissue.

For their initial experiments they used mouse fibroblast cells, finding that their method was efficient at turning these cells into iPS cells and that the transforming genes could be removed afterwards. But were these cells really capable of developing into any cell type? Initial in vitro experiments indicated that they could be differentiated into a kind of nerve cell, and when implanted into mice they formed teratocarcinomas, a type of benign tumour containing cells of different tissue types that is a characteristic product of pluripotent cells such as embryonic stem cells. The next test was to see if these virus-free iPS cells could really differentiate and grow into a wide range of normal healthy tissues, and to do this they turned to chimeric mice, where the iPS cells are combined with normal mouse embryonic cells to produce an embryo that contains a mix of both cells. The resulting chimeric mice were healthy, and the iPS cells were found to have contributed to all major tissue types. This is needless to say an experiment that could not be preformed ethically in humans.

Armed with the knowledge gleaned from their mouse work the team applied their technique to the creation of virus-free iPS cells from human fibroblasts, and succeeded in producing iPS cells that expressed the genetic markers seen in human embryonic stem cells. The rest is newspaper headlines!

Amid the hype it is worth remembering that, as scientists are perhaps overly fond of saying, these are still early days and this approach will require much evaluation and refinement in both animals and in vitro before clinical trials can begin, so as Professor Robin Lovell-Badge pointed out it's certainly not the time to stop research on human embryonic stem cells. It is also worth considering that it is knowledge gained from the study of the embryonic stem cells of humans and animals that furnishes us with the knowledge that enables iPS cell production.

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